Recent papers (last 5 years, selected)
CRISPR/Cas9 editing of APP C-terminus attenuates β-cleavage and promotes α-cleavage. Sun et al., Nature Communications, Jan 2019
Processive flow by biased polymerization mediates the slow axonal transport of actin. Chakrabarty et al., Journal of Cell Biology, Nov 2018
The Nano-Architecture of the Axonal Cytoskeleton. Leterrier C, Dubey P and Roy S. Nature Reviews in Neuroscience , Nov 2017
The physical approximation of APP and BACE-1: A key event in Alzheimer's disease pathogenesis. Sun J and Roy S. Developmental Neurobiology, Nov 2017
Hsc70 chaperone activity is required for the cytosolic slow axonal transport of synapsin. Ganguly et al., Journal of Cell Biology. May 2017
Visualization of APP and BACE-1 approximation in neurons: new insights into the amyloidogenic pathway. Das et al., Nature Neuroscience, Jan 2016
A dynamic formin-dependent deep F-actin network in axons. Ganguly et al., Journal of Cell Biology, Aug 2015
α-Synuclein Multimers Cluster Synaptic Vesicles and Attenuate Recycling. Wang et al., Current Biology, Oct 2014
Activity-induced convergence of APP and BACE-1 in acidic microdomains via an endocytosis-dependent pathway. Das et al., Neuron, Aug 2013
Fast vesicle transport is required for the slow axonal transport of synapsin. Tang et al., Journal of Neuroscience, Sept 2013
Welcome to the Roy Lab
The story of life is the story of movement and transformation. Unlike the static cartoons shown in textbooks, most - perhaps all - biological or pathological phenomena are best understood in the context of movement. Intracellular movement is particularly critical for neurons, with tiny cell bodies where most proteins are made, and elongated processes into which these proteins need to be transported. The Roy lab is generally interested in neuronal trafficking, and we study the phenomena by time-tested process of doing science: iterative learning, looking, and thinking. Learning from previous work by other scientists is usually the starting point of all our projects. To look deeper into neurons, we use a variety of microscopic techniques, including live-cell and sub-diffraction imaging. Molecular or chemical biology tools - such as new fluorescence probes - often allow us to peer ever more closely into cells and see new things, or look at old observations in a new light. Often, technological advances - such as CRISPR/Cas9 gene editing - let us to manipulate systems in ways that were not possible before, inspiring us to ask new questions. Our central mission is to "find new things". Below is a general description of our research interests.
Neuronal trafficking in physiology and neurodegenerative diseases:
Due to their complex geometry and finite sites of bulk protein synthesis (cell-bodies), neurons have evolved elaborate transport and trafficking machinery to deliver proteins into axons and dendrites. How are proteins synthesized in microscopic cell-bodies delivered to their distant sites, and then retained there with precision (for example at the synaptic terminals)? Knowledge into the biology of this process is critical for determining neuronal form and function. Understanding trafficking pathways is often vital to understanding disease pathways as well. For instance, neurodegenerative diseases such as Alzheimer's and Parkinson's are typified by abnormalities in normal trafficking pathways (the amyloid trafficking pathway, alpha-synuclein trafficking at the synapse, etc.). Normal and abnormal trafficking are intertwined, and we cannot understand one, without knowing the other.
A general approach in the lab is to develop cellular models of normal and abnormal biological processes – using whatever tool is necessary for the understanding the question at hand (see http://www.roylab.org/publications.html for list of publications). Current projects include novel uses of CRISPR-Cas9 technology in cellular model-systems of neurodegenerative diseases – particularly Alzheimer’s disease; development and application of new tools (including super-resolution microscopy and optogenetics) to explore a mysterious phenomenon called slow axonal transport, and intricacies of the neuronal cytoskeleton (particularly actin); and use of stem cells to explore human cell biology. A guiding philosophy in the lab is to use whatever tools are needed to explore the question at hand, and whenever necessary, build new ones.
The lab has ongoing collaborations with researchers around the world, and also at the Wisconsin Institute for Discovery (WID), the Waisman Center, the Wisconsin Alzheimer’s Center, as well as several other investigators at UW-Madison; and is located on state of the art laboratory and office space overlooking lake Mendota (within the Wisconsin Institute for Medical Research or WIMR-II tower: WIMR-II-science-without-walls).